Abdominal adiposity and cardiometabolic risk factors in children and adolescents: A Mendelian randomization analysis

Anna Viitasalo; Theresia Maria Schnurr; Niina Pitkänen; Mette Hollensted; Tenna R H Nielsen; Katja Pahkala; Mustafa Atalay; Mads Vendelbo Lind; Sami Heikkinen; Christine Frithioff-Bøjsøe; Cilius E Fonvig; Niels Grarup; Mika Kähönen; Germán D Carrasquilla; Anni Larnkjær; Oluf Pedersen; Kim F. Michaelsen; Timo A Lakka; Jens-Christian Holm; Terho Lehtimäki; Olli Raitakari; Torben Hansen; Tuomas Oskari Kilpeläinen

doi:10.1093/ajcn/nqz187

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: A Mendelian randomization analysis

Anna Viitasalo, Theresia Maria Schnurr, Niina Pitkänen, Mette Hollensted, Tenna R H Nielsen, Katja Pahkala, Mustafa Atalay, Mads Vendelbo Lind, Sami Heikkinen, Christine Frithioff-Bøjsøe, Cilius E Fonvig, Niels Grarup, Mika Kähönen, Germán D Carrasquilla, Anni Larnkjær, Oluf Pedersen, Kim F. Michaelsen, Timo A Lakka, Jens-Christian Holm, Terho LehtimäkiOlli Raitakari, Torben Hansen, Tuomas Oskari Kilpeläinen

8 Citationer (Scopus)

Abstract

Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear.

Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization.

Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHR_adjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y.

Results: WHR_adjBMI GRS was associated with higher WHR_adjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHR_adjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHR_adjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal.

Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

Originalsprog	Engelsk
Tidsskrift	American Journal of Clinical Nutrition
Vol/bind	110
Udgave nummer	5
Sider (fra-til)	1079-1087
Antal sider	9
ISSN	0002-9165
DOI	https://doi.org/10.1093/ajcn/nqz187
Status	Udgivet - 1 nov. 2019

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10.1093/ajcn/nqz187

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Viitasalo, A., Schnurr, T. M., Pitkänen, N., Hollensted, M., Nielsen, T. R. H., Pahkala, K., Atalay, M., Lind, M. V., Heikkinen, S., Frithioff-Bøjsøe, C., Fonvig, C. E., Grarup, N., Kähönen, M., Carrasquilla, G. D., Larnkjær, A., Pedersen, O., Michaelsen, K. F., Lakka, T. A., Holm, J-C., ... Kilpeläinen, T. O. (2019). Abdominal adiposity and cardiometabolic risk factors in children and adolescents: A Mendelian randomization analysis. American Journal of Clinical Nutrition, 110(5), 1079-1087. https://doi.org/10.1093/ajcn/nqz187

Viitasalo, A, Schnurr, TM, Pitkänen, N, Hollensted, M, Nielsen, TRH, Pahkala, K, Atalay, M, Lind, MV, Heikkinen, S, Frithioff-Bøjsøe, C, Fonvig, CE, Grarup, N, Kähönen, M, Carrasquilla, GD, Larnkjær, A , Pedersen, O , Michaelsen, KF, Lakka, TA, Holm, J-C, Lehtimäki, T, Raitakari, O, Hansen, T & Kilpeläinen, TO 2019, 'Abdominal adiposity and cardiometabolic risk factors in children and adolescents: A Mendelian randomization analysis', American Journal of Clinical Nutrition, bind 110, nr. 5, s. 1079-1087. https://doi.org/10.1093/ajcn/nqz187

@article{0c2cc1a25e12415db3c437df9215d17b,

title = "Abdominal adiposity and cardiometabolic risk factors in children and adolescents: A Mendelian randomization analysis",

abstract = "Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear.Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization.Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y.Results: WHRadjBMI GRS was associated with higher WHRadjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal.Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.",

keywords = "Faculty of Science, Abdominal adiposity, Children, Waist-to-hip ratio, Cardiovascular disease risk, Cardiometabolic risk, Mendelian randomization, Meta-analysis, ALSPAC",

author = "Anna Viitasalo and Schnurr, {Theresia Maria} and Niina Pitk{\"a}nen and Mette Hollensted and Nielsen, {Tenna R H} and Katja Pahkala and Mustafa Atalay and Lind, {Mads Vendelbo} and Sami Heikkinen and Christine Frithioff-B{\o}js{\o}e and Fonvig, {Cilius E} and Niels Grarup and Mika K{\"a}h{\"o}nen and Carrasquilla, {Germ{\'a}n D} and Anni Larnkj{\ae}r and Oluf Pedersen and Michaelsen, {Kim F.} and Lakka, {Timo A} and Jens-Christian Holm and Terho Lehtim{\"a}ki and Olli Raitakari and Torben Hansen and Kilpel{\"a}inen, {Tuomas Oskari}",

note = "CURIS 2019 NEXS 297 Copyright {\textcopyright} American Society for Nutrition 2019.",

year = "2019",

month = nov,

day = "1",

doi = "10.1093/ajcn/nqz187",

language = "English",

volume = "110",

pages = "1079--1087",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "American Society for Nutrition",

number = "5",

}

TY - JOUR

T1 - Abdominal adiposity and cardiometabolic risk factors in children and adolescents

T2 - A Mendelian randomization analysis

AU - Viitasalo, Anna

AU - Schnurr, Theresia Maria

AU - Pitkänen, Niina

AU - Hollensted, Mette

AU - Nielsen, Tenna R H

AU - Pahkala, Katja

AU - Atalay, Mustafa

AU - Lind, Mads Vendelbo

AU - Heikkinen, Sami

AU - Frithioff-Bøjsøe, Christine

AU - Fonvig, Cilius E

AU - Grarup, Niels

AU - Kähönen, Mika

AU - Carrasquilla, Germán D

AU - Larnkjær, Anni

AU - Pedersen, Oluf

AU - Michaelsen, Kim F.

AU - Lakka, Timo A

AU - Holm, Jens-Christian

AU - Lehtimäki, Terho

AU - Raitakari, Olli

AU - Hansen, Torben

AU - Kilpeläinen, Tuomas Oskari

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear.Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization.Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y.Results: WHRadjBMI GRS was associated with higher WHRadjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal.Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

AB - Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear.Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization.Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y.Results: WHRadjBMI GRS was associated with higher WHRadjBMI (β = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: β = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: β = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: β = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (β = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (β = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal.Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

KW - Faculty of Science

KW - Abdominal adiposity

KW - Children

KW - Waist-to-hip ratio

KW - Cardiovascular disease risk

KW - Cardiometabolic risk

KW - Mendelian randomization

KW - Meta-analysis

KW - ALSPAC

U2 - 10.1093/ajcn/nqz187

DO - 10.1093/ajcn/nqz187

M3 - Journal article

C2 - 31504107

SN - 0002-9165

VL - 110

SP - 1079

EP - 1087

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 5

ER -

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: A Mendelian randomization analysis

Abstract

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